European Thyroid Journal最新文献

Primary congenital hypothyroidism (CH) is the most common neonatal endocrine disorder, and may be etiologically subdivided into thyroid dysgenesis (TD), referring to abnormal thyroid development, and dyshormonogenesis, where a defective thyroid hormone biosynthesis pathway results in inadequate hormone production despite a structurally intact gland. Delayed treatment of neonatal hypothyroidism may result in irreversible neurodevelopmental impairment; therefore, where available, CH screening programs facilitate prompt diagnosis. However, the molecular basis for CH remains unclear in the majority of cases. This review summarizes current understanding of the genetic etiologies underlying primary CH and associated phenotypes. Classical genetic causes are discussed in the context of their role in normal thyroid physiology. Genes recently reported to play a role in the pathogenesis of CH are discussed, and novel genomic mechanisms in CH are described.

Introduction: Insulin resistance (IR) is a phenomenon commonly observed in pregnancy. Increased insulin concentrations might impact thyroid function and structure during gestation.

Objectives: This study investigates the bidirectional relationship between IR indices and thyroid function and morphology in pregnant women.

Methods: In 1069 gravid participants of the Polish National Programme for Elimination of Iodine Deficiency (2007-2017), blood samples were analyzed for TSH, FT3, FT4, aTPO, fasting glucose, and insulin concentrations, and the thyroid structure was assessed with ultrasound (in 1065 subjects). Based on calculated Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) values, participants were stratified into two subgroups: HOMA-nl (HOMA-IR <2.5) and HOMA-h (HOMA-IR ≥2.5) comprising 894, and 175 women, respectively.

Results: Significant difference in mean TSH (1.77 ± 1.17 vs 1.96 ±1.04; P=0.008) and mean FT4 (12.65± 2.3 vs 11.47±1.9; P=0.001) concentrations between HOMA-nl and HOMA-h groups was found. The subgroups did not differ in thyroid nodularity or multinodular goiter prevalence. HOMA-IR positively correlated with TSH concentrations, BMI, and thyroid volume. Serum FT3 and FT4 concentrations showed negative correlations with HOMA-IR.

Conclusions: IR seems to affect the thyroid function of gravid women by diminishing the ability to respond to increased thyroid hormones (TH) demand. Thyroid volume increase during pregnancy may be influenced by IR, however, its short-term effect on thyroid nodularity appears to be negligible.

Metastatic differentiated thyroid cancer (DTC) is responsible for most thyroid cancer-related deaths, with an even worse prognosis for patients with radioactive iodine (RAI)-refractory DTC (RAIR-DTC). While multi-kinase inhibitors (MKIs) and tyrosine kinase inhibitors (TKIs) offer effective treatments for RAIR-DTC, most patients remain noncurative and eventually experience disease progression. Additionally, long-term use of these medications is hindered by adverse events, drug resistance, and high cost. Recently, the use of MKIs and TKIs has reignited interest in enhancing RAI incorporation. This approach aims to restore the effectiveness of RAI therapy in patients with RAIR-DTC by using agents that increase RAI uptake, potentially overcoming current treatment challenges. This review covers the molecular mechanisms behind RAI resistance, the definition of RAIR-DTC, and the efforts to enhance RAI incorporation through various agents, including those currently undergoing clinical trials.

Background: Management of benign nodular thyroid disease (BNTD) has changed dramatically over the past two decades as reflected by international guidelines recommendations.

Purpose: We sought to document the preferences regarding the management of euthyroid BNTD among thyroid dedicated members of the Spanish Society of Endocrinology and Nutrition (SEEN) and assess the extent to which present international guidelines recommendations have been incorporated into ordinary practice.

Methods: Online survey on the management of a standard case of BNTD among SEEN thyroid experts and explore of variations in management following different clinical scenarios in which variables such as sex, age, ultrasound characteristics, fine needle aspiration results or patient preferences change.

Results: Two hundred and eleven (9% of the SEEN members) participated in the survey. Most of them, 147 (69.7%), recommended periodic monitoring, 43 (20.3%) surgery and 21 (10.0%) minimally invasive procedures (MIP). No participant opted for levothyroxine or radioiodine. Management of BNTD was modified based on patient preferences, both in favour of more aggressive (surgery) and more conservative (MIP or monitoring) options.

Conclusions: The vast majority of Spanish thyroidologists followed the international guidelines recommendations for BNTD management. The trend shows the positive impact of the guidelines' recommendations with a shift towards more conservative management and taking into account patient preference as a binding element in therapeutic decision-making.

Introduction: This case report aims to discuss the development of fatal lung fibrosis in a young boy following treatment of metastasized differentiated thyroid carcinoma (DTC).

Case presentation: A 3.6-year-old boy was diagnosed in year 1995 with papillary thyroid carcinoma with extensive metastases. He underwent total thyroidectomy and received multiple courses of radioactive iodine (RAI) therapy between September 1995 and February 1998. The patient received six courses of RAI therapy within 30 months, cumulatively amounting to 10 GBq 131I, in response to significantly elevated thyroglobulin levels and morphologically persistent miliary lung metastases. Despite the significant regression of his metastatic disease, the patient exhibited progressive lung fibrosis 2.75 years after the sixth RAI therapy. This condition ultimately led to respiratory failure and resulted in the patient's death 6.7 years following the initial diagnosis.

Discussion/conclusion: This case highlights the potential severe complications associated with several courses of RAI therapy in young children suffering from extensive lung metastases and underscores the need for careful treatment planning and long-term monitoring. Given the risks of RAI therapy, particularly the risk of fatal lung fibrosis, it is crucial to tailor RAI therapy carefully, especially in young patients. Notably, thyroglobulin levels can decrease even after cessation of RAI therapy, indicating that levels immediately post-therapy are not necessarily representing the development of the response over the following months.

Congenital hypothyroidism (CH) is defined as thyroid hormone deficiency at birth and constitutes one of the most common causes of preventable intellectual disability worldwide. Central CH is caused by insufficient pituitary or hypothalamic control of thyroid function, biochemically characterized by a low serum free thyroxine (fT4), in combination with a low, normal or mildly elevated thyroid-stimulating hormone (TSH). Central CH is less common than primary CH and is part of multiple pituitary hormone deficiencies (MPHD) in most of the cases. MPHD at birth, also known as 'congenital hypopituitarism', is a potentially life-threatening condition due to the possible co-occurrence of adrenocorticotropin hormone and growth hormone deficiency that can result in severe hypoglycemia and adrenal crisis. To date, central CH is the only pituitary hormone deficiency suitable for newborn screening (NBS), providing an opportunity for early detection of MPHD. Even though the first NBS programs utilized T4-based methods that were able to identify central CH, most countries have since transitioned to TSH-based approaches due to the high rate of false positives associated with T4-based strategies. Now, 50 years after the introduction of NBS for CH, only a few countries around the world have a screening program capable of detecting central CH. In this paper, we review the past, present and future of NBS for central CH. We will outline the importance of early detection of central CH and discuss the challenges and opportunities of screening for this condition.

Objective: In the general population, women pregnant with a male fetus (MF) have a higher prevalence of gestational diabetes mellitus (GDM) compared with those pregnant with a female fetus (FF). Some studies suggest a higher prevalence of GDM in euthyroid pregnant women with thyroid autoimmunity (TAI+) compared with women without TAI (TAI-). However, whether the impact of TAI on GDM correlates with fetal gender has not been documented.

Design/methods: A single-center cohort study including 1201 women who were screened at a median of 12 (11-14) weeks of pregnancy for thyroid disorders (TSH, free T4 and thyroid peroxidase antibodies (TPOAb)) and at 24-28 weeks for GDM with an oral glucose tolerance test. Exclusion criteria were pre-pregnancy diabetes or hypertension, thyroid dysfunction (treated or untreated) before and after screening, thyroid screening after 20 weeks of pregnancy and assisted pregnancies. The diagnosis of GDM was based on the 2013 WHO criteria, and that of TAI by increased TPOAb levels (≥60 kIU/L).

Results: Overall, 622 women were expecting a FF (51.8%) and 579 a MF (48.2%). Seventy-five women were TAI+ (6.2%). The overall prevalence of GDM was 19.6%, 28% in TAI+ women and 19% in TAI- women (P = 0.008 after adjustment for confounders). In women who were expecting a FF, the prevalence of GDM was 34.4% in TAI+ women vs 19.2% in TAI- women; P = 0.002.

Conclusions: The prevalence of GDM was increased in euthyroid TAI+ women, but only in the case of pregnancies with a FF. This is opposite to the result observed in the general population and deserves more research to explore the underlying mechanisms.

Objective: To evaluate the current quality of thyroid ultrasound reports in the Community of Madrid.

Methods: Consecutive thyroid ultrasound reports from patients evaluated in the endocrine outpatient clinics of eight academic hospitals in the Community of Madrid were assessed for quality during 2021 and 2022. Descriptions of eight different features were evaluated: number and axes of dimensions, composition, echogenicity, margins, shape, calcifications and category of suspicion. Features were considered adequately reported if described for all nodules ≥1 cm. The number of correctly reported features was compared by year of data capture (2021 vs 2022), specialty of the informant (radiologist vs endocrinologist), and origin of the report (in-house vs outsourced center). The quality of reports for assessing the need for cytological evaluation and/or growth during follow-up was evaluated.

Results: A total of 1234 reports were included, 63% from 2021; 82% were issued by radiologists and 89% were issued in-house. Composition and echogenicity were the most frequently reported (79% and 72%, respectively). The rest of the features were appropriately described in less than half of the reports. Forty percent of the reports were good to select nodules for biopsy, 23% had sufficient data to assess growth during follow-up, and only 13% met both quality criteria. The overall quality of reports was worse in outsourced centers (median number of described features 2 vs 4, P < 0.001) and better when issued by endocrinologists (median number of described features 6 vs 3, P < 0.001).

Conclusions: Most thyroid ultrasound reports issued in the Community of Madrid provide insufficient data to make management decisions regarding thyroid nodules.

The development of mouse models for thyroid cancer has significantly advanced over the years, enhancing our understanding of thyroid tumorigenesis, molecular pathways and treatment responses. The earliest mouse models of thyroid cancer relied on hormone, radiation or chemical carcinogenesis to induce tumors. However, as our understanding of the genetic alterations driving thyroid cancer has expanded, more sophisticated genetic engineering techniques have been employed to create models with thyroid-specific expression of these driver mutations. While driver mutations can initiate tumorigenesis, they are often insufficient to sustain cancer progression and invasion, which significantly limits their usefulness in studying advanced thyroid cancers. Recent studies exploring the genomic landscape of advanced thyroid cancer have identified several cooperating mutations, which are secondary genetic alterations that work alongside driver mutations to promote thyroid tumor progression. Indeed, mice with a combination of oncogenic drivers and common cooperating alterations have been developed, demonstrating that these alterations function in conjunction with the oncogenic driver to promote the progression to advanced thyroid cancer. These models provide important preclinical tools to explore how cooperating alterations influence the response to therapies, particularly those targeting the oncogenic driver. This review will focus on recent publications that broaden the scope of advanced thyroid cancer models by combining thyroid-specific oncogenic driver expression with various cooperating mutations.

Thyroid hormone (TH) is essential for brain development in utero and during the first 2 to 3 years of life. The negative effects of TH deficiency on brain development are irreversible. Early detection of TH deficiency in neonates (congenital hypothyroidism (CH) through newborn screening (NBS)) allows for early treatment, thereby preventing brain damage. Screening for CH began in 1973 with the measurement of total thyroxine (T4) in dried blood spots. The enhanced sensitivity of thyroid-stimulating hormone (TSH) measurement has prompted a shift in the approach to NBS for CH. Currently, worldwide, the majority of NBS programs for CH employ TSH as the primary screening marker. However, a select few programs still utilize T4 as the primary marker, enabling the detection of both primary and central CH. This review provides an overview of the laboratory aspects of the screening on CH from the start of screening to the present.